This investigator has proposed an hypothesis to explain physical dependence on ethanol (ETOH), based on the concept that ETOH can serve as an indirect energy source for the brain, and that the presence of the ethanol-derived energy providing moieties reduced the synthesis of normal carbohydrate and lipid-derived metabolites. The brain could then be said to be physically dependent on ETOH-derived energy-providing moieties (primarily acetate, BOHB and AcAc) in NADH and Acetyl-CoA. The specific aim of this research is to determine the time course of changes in levels of ETOH, glucose, glycogen, acetate, BOHB and AcAc in liver, blood, and brain of DBA/2J and C57BL/6J mice at times of acquisition of and during physical dependence on ETOH and at times durin varying stages of withdrawal. Proposed Research. DBA/2J and C57BL/6J mice, 60 days of age, will be made physically dependent on ethanol using the Carnation Liquid Slender diet method. Mice will be sacrificed in liquid nitrogen; 10 to 25 mg samples of blood, brain, and liver will be taken and assayed enzymically - flourimetrically for the metabolites named above at various times (2,4, or 6 days) after the onset of the liquid diet. Other mice will be withdrawn from the diet after physical dependence has been established, and sacrificed at various times (2,5,6,7,8,9 or 10 hrs.) post-withdrawal. The intended accomplishments of this research are to utilize a highly controlled laboratory model for research on CNS reactivity (a) to test this investigator's hypothesis that ethanol can serve as an indirect source of energy for the brain, (b) to measure the time course of changes induced by ethanol in the levels of the major energy-providing metabolites in liver, blood, and brain, (c) to provide another test of this investigator's hypothesis that susceptibility to audiogenic seizures (in this case observed during withdrawal) is due to a reduction in the brain energy reserve pool, and (d) to begin to establish a viable ethanol-research program in this laboratory. The information to be generated by this research may begin to provide data on the sequence of changes which culminate in an altered system characterized by withdrawal symptoms on removal of ethanol.